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Case study1

Spinal neurobrucellosis is an unusual cause of2

nontraumatic paraplegia in Zaria, Northern3

Nigeria: A report of 3 cases and review of current4

literature.5

OR Obiako, SA Abubakar, JA Kehinde, EU6

Iwuozo, AU Hamidu1.7

Neurology Unit, Department of Medicine,8

Radiology1, Ahmadu Bello University Teaching9

Hospital (ABUTH) Zaria10

Correspondence: Dr OR Obiako,11

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Running title: report of spinal neurobrucellosis as14

an unusual cause of nontraumatic paraplegia15

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1819202122

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SUMMARY25

Background and Objective: Brucellosis is a zoonotic febrile infection common among farmers26

or herdsmen who come into contact with animals or animal products. Neurological27

complications are uncommon, but when they occur can be confused with other neurological28

diseases, particularly those due to tuberculosis. This report is intended to remind health workers29

and people living in Brucella endemic communities that spinal neurobrucellosis can mimic Potts’30

disease as the cause of nontraumatic paraparesis or paraplegia.31

Patients and materials: We report the cases of three patients who presented with paraplegia32

following months of constitutional symptoms of fever, headache, malaise and weight loss. All33

were exposed to cows and goats and sheep. One patient had received antituberculous therapy for34

18 months with minimal recovery. Serology and neuroimaging were used to confirm the35

diagnosis.36

Result: All the patients recovered within 6 to 12 weeks of rifampicin, doxycycline,37

trimethoprim-sulfamethoxazole or streptomycin, but with residual paraparesis.38

Conclusion: spinal neurobrucellosis can be confused with Pott’s disease with consequent poor39

treatment outcome.40

Keywords: spinal neurobrucellosis, zoonosis, paraplegia, serology, neuroimaging41

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Introduction48

Brucellosis, also called Malta fever or Mediterranean fever (it was first described in Malta in the49

Mediterranean region) is caused by intracellular gram-negative bacteria of the genus Brucella. It50

is the most common zoonosis in the world, accounting for the annual occurrence of more than51

500,000 cases1. All Brucella infections are caused by direct or indirect exposure to animals or52

animal products (e.g., milk, milk products and raw meat), although possibility of aerosolized53

person to person transmission exist. Human disease is caused by any four species: Brucella54

melitensis (affecting goats, sheep, camel); Brucella abortus (cattle); Brucella suis (pigs, hogs)55

and Brucella canis (dog). Symptoms are variable and non specific because any organ or system56

in the human body can be affected, but the main features are remittent fever which can be57

intermittent, relapsing and undulant in nature. Others are somatic symptoms of headache, body58

pains, night sweats, anorexia, fatigue, malaise, weight loss, and depression. The infection affects59

the reticuloendothelial system primarily, and the most common site is the osteoarticular sites2.60

In endemic areas, isolation of bacteria from serum or cerebrospinal fluid (CSF) is the gold61

standard but appropriate serological tests such as IgG agglutination titers of >1:160 in CSF or62

>1:320 in serum can be diagnostic, particularly if there are rising titers in serial testing3.63

Treatment of neurobrucellosis entails use of triple drugs selected from rifampicin, doxycycline,64

gentamicin, streptomycin, trimethoprim-sulfamethoxazole and ciprofloxacin, usually for periods65

of 6 weeks (streptomycin) and 3 months (for others). Recovery of patients with acute66

neurobrucellosis is typically excellent, but prognosis of chronic neurobrucellosis is variable.67

Clinical improvement as well as improvement in CSF pleocytosis and fall in CSF and68

blood Brucella titers should occur after appropriate treatment. Poor outcomes are associated with69

complications such as raised intracranial pressure, stroke, endocarditis, intracranial mycotic70

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aneurysm and haemorrhage; and osteospondylitis with compressive myelopathy or71

radiculopathy4. Because acute symptoms are similar to many tropical fevers, the infection may72

be misdiagnosed with dare consequences. Therefore, this report is to remind physicians that73

neurobrucellosis is a differential diagnosis of non-traumatic paraplegia, particularly in endemic74

areas.75

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Case Reports77

1. A.R, a 15 year old Fulani milkmaid, who also ingested unpasteurized milk regularly,78

developed intermittent fever of 5-7days intervals, profuse night sweats, anorexia, fatigue,79

malaise and hearing loss for 8 weeks. At the 7th week she developed insidious non- radiating80

band-like, low back pain, and progressive lower limb weakness culminating in paraplegia and81

double incontinence at the 8th week. She therefore became bedbound leading to development of82

multiple gluteal sores and anterior right thigh abscess. At 10th week, she presented to our centre83

when she developed severe tetanus of one day duration.84

On examination, she was chronically ill-looking, asthenic, conscious, but febrile (temperature85

38.7 0 C), diaphoretic and pale. She had multiple gluteal and trochanteric ulcers discharging86

cheesy/putrid materials; and episodic titanic spasms with locked-jaw, trismus, opisthotonus and87

rigidity. She also had spastic paraplegia, bilateral extensor plantar reflexes, scoliosis, and sensory88

level at T12, but no obvious vertebral deformity or gibbus. She was incontinent of both faeces89

and urine, and had a diaper on.90

She was treated with intravenous human tetanus immunoglobulins 10,000 international units91

(I.U) stat after a test dose, metronidazole infusions 500 mg 8 hourly, and intermittent diazepam92

20-40 mg in 5% dextrose saline 8-12 hours until spasm free. She received 3 pints of packed cells93

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blood transfusion, and recovered from tetanus within 2 weeks of admission. She was also94

investigated for brucellosis, found positive and was treated with antibiotics. She recovered and95

was discharged home with residual paraparesis at 12th week of admission. The results of96

laboratory investigations, drug regimen and outcome of treatment are summarized in table 1.97

2. J.N, a 13 year old student developed intermittent fever of 5-7 days intervals, headache, neck98

pain and loss of consciousness for 2 weeks. He was treated for (? Pyogenic) meningitis with99

parenteral ceftriaxole at a private hospital where he first presented; and regained consciousness100

after 10 days. However, the fever continued and he developed paraplegia, urinary retention and101

incontinence within 4 weeks of illness. There was no history of antecedent diarrhea, upper102

respiratory tract infection, or recent vaccination. Eight weeks later, he developed a sinus above103

the gluteal cleft which discharged a cheesy material. He worked in his father’s animal farm104

which consisted of pigs, goats and sheep, but did not ingest unpasteurized milk.105

On examination, he was fully conscious, febrile (temperature 37.60 C), pale and dehydrated. He106

also had nuchal rigidity with positive Brudzinski and Kernig’s signs, flaccid paraplegia, and loss107

of sensation below the knee joints (L 4 and below). There was a sinus which was discharging108

cheesy material from a slit-like opening above the gluteal cleft on the midline. He was109

incontinent of urine, but not of faeces, and there was no obvious vertebral deformity or no110

gibbus.111

He was investigated for brucellosis, found positive and treated with antibiotics. Constitutional112

symptoms of brucellosis resolved within 2 weeks of treatment as shown by the pattern of fever at113

presentation and 15 days after (in figures I and II respectively), but his neurologic deficit114

persisted. He was instructed to continue his drug regimen for 16- 24 weeks but was discharged115

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on request with residual paraparesis at 12th week of therapy. He was lost to follow-up. The116

results of his laboratory tests, drug regimen and outcome of treatment are summarized in table 1.117

3. M.D, a 56 year old man who worked as a veterinary health extension worker in Kaduna State118

Ministry of Agriculture and Animal resources presented with 2 years history of headache,119

anorexia, weight loss, fatigue and progressive lower limb weakness resulting in paraplegia and120

urinary incontinence. He had completed 18 months course of antituberculous therapy for121

suspected Pott’s disease with minimal improvement. His daily routine of more than two decades122

was vaccination of herds of cows, sheep, goats and pigs. He never ingested unpasteurized milk.123

On examination, he was fully conscious, pale, afebrile and mildly wasted. He had spastic124

paraplegia, bilateral extensor plantar reflexes, sensory level at T10, and urinary incontinence.125

There were multiple vertebral deformities and gibbus.126

He was put on anti-brucella therapy after investigations, and within 12 weeks muscle power in127

his lower limbs improved from 0/5 to 3/5. He was instructed to continue his drug regimen for 16-128

24 weeks, but was also lost to follow-up. The details of his laboratory results, drug regimen and129

outcome of treatment are summarized in table 1.130

Discussion131

Northern Nigeria is indigenous to herdsmen and cultures engaged in animal husbandry; and since132

the risk of brucellosis is proportional to the degree of contact with Brucella-infected animals,133

their excreta, or their edible byproducts; the disease is expected to be endemic in our134

environment5. Yet, cases of acute uncomplicated brucellosis are not commonly reported in our135

hospitals. Underreporting may be either because health workers are unfamiliar with the infection,136

or the similarities of its acute constitutional symptoms are confused with those of other tropical137

infectious diseases particularly malaria fever, typhoid fever and tuberculosis6. This may explain138

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why all 3 patients were misdiagnosed at the peripheral hospitals where they first presented before139

they were referred to us because of the complications they developed. Prolonged contact with140

animals and their edible byproducts were main risk factors for the disease in all the patients.141

Neurobrucellosis affecting the central (CNS) or peripheral nervous system (PNS) has been142

described in 3–5% of patients, with a variety of clinical manifestations and imaging143

abnormalities that mimic other neurologic diseases4. Although our patients had similar144

constitutional symptoms and neurological signs, the patterns and extent of spinal cord damage145

were different. In the first and second patients (case 1 and 2), paraplegia was due to146

inflammatory changes in the spinal cord (myelitis & demyelination of white matter), and spinal147

cord and nerve roots (myelitis, demyelination of white matter & polyradiculitis) respectively; in148

the third patient (case 3), osteospondylitic extraaxial compression of the spinal cord (by149

granuloma formation) was responsible. These lesions are said to result from direct or indirect150

immunological processes involving cytotoxic T lymphocytes, microglia and humoral immune151

activation leading. Therefore spinal neuroimaging may be show normal architecture (if lesion is152

early and mild), or abnormal enhancement (for inflammatory changes and demyelinating153

lesions)7.154

An understanding of the behavior of the humoral immune system is important in the diagnosis of155

brucellosis. The level of immunoglobulin M (IgM) antibodies begins to rise at the end of the first156

week of infection, peaks at about one month, and will remain elevated for years; even in the157

absence of active infection. IgA antibodies are elaborated late but may also persist for years. On158

the other hand, IgG antibodies begin to appear at approximately one month of infection, and159

begin to disappear thereafter. Therefore, persistent elevation of IgG antibodies is an indication of160

chronic active infection, or a relapse of the illness8. In our centre, we use the sera of our patients161

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against the IgG antibodies of B melitensis because this organism is the most common cause of162

human brucellosis globally.163

Recovery of Brucella organisms from cultures of CSF or blood is usually very low in164

neurobrucellosis because the organisms are chiefly intracellular in locations, although the CSF165

may exhibit pleocytosis, hypoglycorrhachia, and elevation of protein concentration. The CSF166

findings of this disease can thus mimic those of other intracellular organisms such as167

mycobacteria, fungi and toxoplasma9.168

Rapid diagnosis and treatment often leads to prompt and complete recovery in acute infection,169

but response to appropriate antibiotic is variable in chronic brucellosis. Standard treatment for170

adults with acute spinal brucellosis comprises capsule doxycycline 100 mg BD and tablets171

trimethoprim-sulphamethaxole 960 mg BD, or capsule rifampicin 600 mg for at least 12 weeks,172

combined during the first 3-4 weeks with IM streptomycin. Treatment is prolonged for 18-24173

weeks in chronic neurobrucellosis10.174

In conclusion, neurobrucellosis is a treatable disease with a favorable outcome but the presence175

of complications like meningoencephalitis and myelopathy worsens the prognosis. The disease176

will continue to be an important health problem in developing countries except certain steps are177

taken to reduce its incidence. The steps must include avoidance of unpasteurized dairy products,178

animal contact or improperly cooked meat; regulation of abattoirs; surveillance, culling and179

vaccination of herds of sheep, goats, cows and pigs.180

References181

1. Edwards C, Jawad AS. History of brucellosis. J R Soc Med 2006; 99 (2):54182

2. Young EJ. Human brucellosis. Rev Infect Dis 1983; 5 (5): 821-842183

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3. Young EJ. Serologic diagnosis of human brucellosis: analysis of 214 cases by agglutination184

tests and review of the literature. Rev Infect Dis 1991; 13 (3): 359-372.185

4. Ceran N, Turkoglu R, Erdem I, Inan A, Engin D, Tireli H, et al. Neurobrucellosis: clinical,186

diagnostic, therapeutic features and outcome. Unusual clinical presentations in an endemic187

region. Braz J Infect Dis. 2011; 15 (1): 52-59.188

5. Obiako OR, Ogoina D, Danbauchi SS, Kwaifa SI, Chom ND, Nwokorie E. Neurobrucellosis-189

a case report and review of literature. Niger J Clin Pract 2010; 13 (3): 10-15190

6. Badiaga S, Imbert G, La Scola B. Imported brucellosis associated with plasmodium191

falciparum malaria in a traveler returning from the tropics. J Travel Med 2005; 12 (5): 282-284.192

7. Al-Sous MW, Bohlega S, Al-Kawi MZ, Alwatban J, McLean DR. Neurobrucellosis: clinical193

and neuroimaging correlation. Am J Neuroradiol 2004; 25: 395-401.194

8. Araj GF, Kattar MM, Fattouh LG, Bajakian KO, Kobeissi SA. Evaluation of the PANBIO195

Brucella IgG and IgM enzyme-linked immunosorbent assays for the diagnosis of human196

brucellosis. Clin Diagn Lab Immunol 2005; 12 (11): 1334-1335.197

9. Bouza E, Garcia de la Torre M, Parras F. Brucellar meningitis. Rev Infect Dis 1987; 9 (4):198

810-822.199

10. Alp E, Doganay M. Current therapeutic strategy in spinal brucellosis. Int J Infect Dis 2008;200

12 (6): 573-577201

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Table i. Summary of Laboratory test results, drug regimen, duration of therapy and outcome.203

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Investigations Case 1 Case 2 Case 3

HIV I & II Negative Negative Negative

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Mantoux skin reaction < 5 mm (negative) < 5 mm (negative) < 5 mm (negative)

Chest X ray Normal Normal Normal

Leucocytes

(normal 2-11x10 9/L)

Lymphocytic

pleocytosis

Lymphocytic

pleocytosis

Normal

Hemoglobin

(normal 11- 16 g/dl)

6.9

(severe anemia)

10.2

(mild anemia)

14.0

(normal)

Initial Brucella abortus IgG

serology

1/320 1/320 1/320

Brucella abortus IgG

serology 4 weeks & 12

weeks respectively

1/16, <1/16 1/16, < 1/16 1/64, 1/16

CSF analysis

*Relative to random blood

sugar

Pleocytosis, markedly elevated protein,

lymphocytosis, *hypoglycorrhachia

Lumbar puncture

was constrained by

vertebral spine

deformities

CSF culture Negative Negative Not done

Histopathology of cheesy

material

Non caseating

granuloma

Non caseating

granuloma

Not applicable

Spinal MRI Figure III(area of

hyper-intensity on a

segment of spinal

cord)

Figure IV(areas of

hyper-intensities on

many segments of

spinal cord & spinal

nerve roots)

Not done

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Spine vertebral X ray Normal Normal Destruction of

intervertebral discs

and vertebral bones

T12, L1, L2

Diagnosis Transverse myelitis Transverse myelitis

and polyradiculitis

Osteospondylitic

extraaxial

compressive

myelopathy

Drugs and duration of therapy• 12 weeks of caps

rifampicin 450 mg

daily, doxycycline

100mg BD and tabs

trimethoprim-

sulphamethaxole

960 mg BD.

• To continue

regimen for 16

weeks

• Intramuscular

streptomycin 750

mg daily for 4

weeks, caps

rifampicin 450 mg

daily for 12 weeks,

and caps

doxycycline 100

mg BD for 12

weeks.

• To continue

regimen for 16-24

weeks

•

• Intramuscular

streptomycin 1 gram

daily for 12 weeks,

caps rifampicin 600

mg daily for 24

weeks, and caps

doxycycline 100 mg

BD for 24 weeks.

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Outcome Discharged home

on walking frame

(lower limbs

muscle power 4/5)

at 12 weeks

Discharged home

on wheelchair

(lower limbs

muscle power 3/5)

at 12 weeks

Discharged home on

wheelchair (lower

limbs muscle power

3/5) at 12 weeks

205

206

207

208

Figure 1. Undulant and intermittent temperature pattern before treatment (case 2)209

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211

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Outcome Discharged home

on walking frame

(lower limbs

muscle power 4/5)

at 12 weeks

Discharged home

on wheelchair

(lower limbs

muscle power 3/5)

at 12 weeks

Discharged home on

wheelchair (lower

limbs muscle power

3/5) at 12 weeks

206

207

208

209

Figure 1. Undulant and intermittent temperature pattern before treatment (case 2)210

211

212

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Outcome Discharged home

on walking frame

(lower limbs

muscle power 4/5)

at 12 weeks

Discharged home

on wheelchair

(lower limbs

muscle power 3/5)

at 12 weeks

Discharged home on

wheelchair (lower

limbs muscle power

3/5) at 12 weeks

207

208

209

210

Figure 1. Undulant and intermittent temperature pattern before treatment (case 2)211

212

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212

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Figure 2. Normal temperature pattern after 15 days of treatment (case 2)214

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Figure 3. Coronal view of T2 weighted spinal MRI showing area of218

hyperintensity on a segment of the cord.219

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Figure 4. Sagittal view of T2 weighted spinal MRI showing areas of hyper222

intensities on many segments of the spinal cord and spinal nerve roots223

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